Antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract and underlying mechanisms

Periplaneta americana is a common traditional Chinese medicinal material which has been used to treat arthritis, fever, aches, pains, and inflammation of the extremities for several hundred years. However, little scientific data exists in literature to support its use. The purpose of this study was to evaluate the antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract (PAE) and explore its underlying mechanism. The antipyretic, anti-inflammatory and analgesic activities were evaluated by LPS-induced fever, carrageenan-induced paw edema, abdominal writhing, hot plate and formalin tests, respectively. The mechanism of action was explored by antioxidant activity analysis, inflammatory cytokines expression and febrile mediator measurement, and pathway activation analysis. The results from UHPLC-HRMS indicated that the extract was found to contain dopamine, coumarin, dipeptide, vitamin, organic acid, amino acid and its metabolites, and other organic compounds. PAE showed in a dose-dependent manner antioxidant activity and reduced the protein production and mRNA expression of NO, IL-1β, IL-6, and TNF-α in RAW 264.7 cells in vitro. Moreover, PAE significantly and dose-dependently inhibited the writhing responses and licking time in formalin tests, increased response latency in the hot plate test, reduced carrageenan-induced paw edema and inflammation in mice, decreased LPS-induced rT increase in rats. Furthermore, PAE treatment markedly inhibited the increase in the levels of NO, IL-6, IL-1β, TNF-α, PGE2 and cAMP in plasma of fevered rat, greatly suppressed the activation of inflammatory response pathway and the change of MDA and GSH concentration, MPO and SOD activity as well as FRAP capacity in paw induced by carrageenan injection. In conclusion, the findings suggested that PAE produced potential antinociceptive, anti-inflammatory and antipyretic effects by reducing production of endogenous inflammatory mediators and blocking the MAPK/NF-κB signaling pathway which support the claim for its traditional use in the treatment of various diseases.